Montelukast versus salmeterol in patients with asthma and exercise-induced bronchoconstriction

doi:10.1016/S0091-6749(99)70322-2

Journal of Allergy and Clinical Immunology

Volume 104, Issue 3, September 1999, Pages 547-553

https://doi.org/10.1016/S0091-6749(99)70322-2 Get rights and content

Abstract

Background: Montelukast, a leukotriene receptor antagonist, and salmeterol, a long-acting β₂ -receptor agonist, each have demonstrated benefits in the treatment of exercise-induced bronchoconstriction (EIB) in short-term studies. Direct comparisons between these agents in long-term studies are limited. Objective: We sought to compare montelukast and salmeterol in the long-term treatment of EIB. Methods: One hundred ninety-seven patients with mild asthma and a postexercise fall in FEV₁ of at least 18% were randomized (double-blind) to receive montelukast 10 mg once daily or salmeterol 50 μg twice daily for 8 weeks. Exercise challenge was repeated at day 3, week 4, and week 8 after randomization near the end of the dosing interval for both drugs. The primary efficacy endpoint was the maximal percent fall in postexercise FEV₁ at week 8. Results: Montelukast was effective in treating EIB without inducing tolerance and provided superior (P ≤ .001) protection than salmeterol at weeks 4 and 8, with comparable protection at day 3. The frequency of respiratory clinical adverse events (P = .046) and discontinuations because of clinical adverse events (P = .052) were less with montelukast. Conclusion: The effect of montelukast was greater than that of salmeterol in the chronic treatment of EIB over a period of 8 weeks in patients with mild asthma as demonstrated by effect size, maintenance of effect, and fewer respiratory clinical adverse events during the study period. Montelukast may be a better alternative to salmeterol as a controller agent for the chronic treatment of EIB. (J Allergy Clin Immunol 1999;104:547-53.)

Section snippets

METHODS

Three hundred thirty-three patients with a clinical history of mild asthma for at least 1 year (males and females, aged 14 to 45 years) were screened at 25 centers in 12 countries. Patients had an improvement in FEV₁ of at least 12% after administration of a β-agonist (68% of patients) or airway hyperresponsiveness (defined by a PC₂₀ in FEV₁ in response to ≤4 mg/mL of methacholine or histamine) within the previous 6 months. They were in good health except for asthma and were nonsmokers for at

RESULTS

One hundred ninety-seven patients were randomized to study medication: 102 to montelukast and 95 to salmeterol (Table I).

. Baseline demographics of randomized patients

Characteristic	Montelukast (n = 102)	Salmeterol (n = 95)
Age, y (range)	27 (15-45)	27 (14-45)
<18 y	8 (8%)	8 (8%)
≥18 to 45 y	94 (92%)	87 (92%)
Sex
M	53 (52%)	45 (47%)
F	49 (48%)	50 (53%)
Race
White	77 (75%)	71 (75%)
Asian	2 (2%)	1 (1%)
Mixed race	23 (23%)	23 (24%)
Duration of asthma, y (SD)	15.4 (8.8)	13.0 (9.2)
Pre-exercise FEV₁ % predicted (SD)	86.6 (13.7)	87.2

DISCUSSION

We found that montelukast had a greater effect than salmeterol in the chronic treatment of EIB over 8 weeks. Protection by montelukast was evident by day 3 and persisted throughout the 8-week treatment period without development of tolerance. All 3 exercise endpoints supported this conclusion. Similarly, other montelukast studies in chronic asthma also support the lack of tolerance to treatment.17, 18, 19, 20 The effects with montelukast were comparable to those seen in previous exercise

Acknowledgements

We thank Cecile Dubois, MSc, and William Malbecq, PhD, for statistical advice and Veerle Coenen and Pam Dellea for coordination of study data. We also gratefully acknowledge the excellent study monitors, investigators and patients.

The members of the Montelukast/Salmeterol Exercise Study Group also included: A. Ahonen, MD, PhD; A. Bergmann, MD; N. P. Boye, MD; M. G. Britton, MB; R. Carter, MBBCh; J. P. H. M. Creemers, MD; M. Decramer, MD, PhD; P. N. R. Dekhuijzen, MD, PhD; J. P. Finnerty, MB; L.

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^☆: *A list of the members of the Montelukast/Salmeterol Exercise Study Group can be found in the “Acknowledgments” section.

^☆☆: †This paper is dedicated to Dr Jay Jasan who died in September 1998.

^★: Supported by a grant from Merck & Co, Inc, Whitehouse Station, NJ.

^★★: Reprint requests: Jonathan A. Leff, MD, Merck & Co, Inc, One Merck Drive, PO Box 100, WS2BC-25, Whitehouse Station, NJ 08889-0100.

^♢: 0091-6749/99 $8.00 + 0 1/1/99997

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Montelukast versus salmeterol in patients with asthma and exercise-induced bronchoconstriction☆,☆☆,★,★★,♢

Abstract

Section snippets

METHODS

RESULTS

DISCUSSION

Acknowledgements

J Allergy Clin Immunol

Respir Med

Chest

J Pediatr

J Allergy Clin Immunol

J Allergy Clin Immunol

Ann Allergy Asthma Immunol

Lancet

Exercise-induced asthma: state of the art

Chest

Effect of regular inhaled beclomethasone on exercise and methacholine airway responses in school children with recurrent wheeze

Eur Respir J

Exercise-induced asthma: an assessment of current etiologic concepts

Chest

An inhaled glucocorticoid does not prevent tolerance to the bronchoprotective effect of a long-acting inhaled β2-agonist

Am J Respir Crit Care Med

The effect of regular inhaled albuterol on exercise-induced bronchoconstriction

Am J Respir Crit Care Med

Increased urinary excretion of LTE4 after exercise and attenuation of exercise-induced bronchospasm by montelukast, a cysteinyl leukotriene receptor antagonist

Thorax

Inhibition of exercise-induced bronchoconstriction by MK-571, a potent leukotriene D4 -receptor antagonist

N Engl J Med

Dose-related protection of exercise bronchoconstriction by montelukast, a cysteinyl leukotriene-receptor antagonist, at the end of a once-daily dosing interval

Clin Pharmacol Ther

The protective effect of inhaled leukotriene D4 receptor antagonist ICI 204,219 against exercise-induced asthma

Am Rev Respir Dis

Increased urinary excretion of LTE₄ after exercise and attenuation of exercise-induced bronchospasm by montelukast, a cysteinyl leukotriene receptor antagonist

Inhibition of exercise-induced bronchoconstriction by MK-571, a potent leukotriene D₄ -receptor antagonist

The protective effect of inhaled leukotriene D₄ receptor antagonist ICI 204,219 against exercise-induced asthma